Neural stem cells (NSCs) show a remarkable ability to migrate throughout the CNS, intermingle with host cells, and express foreign transgenes following transplantation. Intriguingly, this inherent migratory property of NSCs emulates the migratory pattern of some brain tumors, such as gliomas, characterized by invasive single cell migration. Potentially, the migratory properties of NSCs can be harnessed to disseminate therapeutic genes products to invading brain tumor cells. As the first step toward this goal, results from phase I studies demonstrated that human NSCs displayed significant tumor targeting migratory behavior toward gliomas while stable expressing a reporter gene. Phase II entails genetically modifying NSCs to express an array of therapeutic genes, and then assessing their potential to target tumor cells and elicit an anti-tumor response. It is anticipated that genetically modified NSCs will infiltrate the tumor mass, track individual tumor cells, and stably express oncolytic proteins that can destroy the cancerous cells in rodent models. These studies will advance the development of a potentially revolutionary treatment strategy using human NSCs as a novel, efficient delivery vehicle to target therapeutic genes to refractory brain tumors. PROPOSED COMMERCIAL APPLICATIONS: Neural stem cells represent a compelling new technology platform for the treatment of neurological diseases. Their natural migratory capacity provides a powerful vehicle to target therapeutic agents directly to refractory brain tumors. This project will evaluate an array of therapeutic genes to expedite the development of a potentially revolutionary cancer therapy strategy to treat deadly brain tumors.